The Neural Basis of Social Cognition and Its Relationship to Social Functioning in Young People at Risk for Schizophrenia

These three studies seek to contribute to the neurological characterization of the development of schizophrenia as well as begin to branch into understanding how neuroanatomical structure and function may relate to specific deficits in social cognition and social functioning within in this population. Paper #1 investigates the relationship between brain structure in young adults at clinical high risk for schizophrenia and social functioning. Paper #2 expands upon the findings of paper #1 by looking at brain structure, social cognition, and social functioning in children and risk for psychosis. Finally, paper #3 focuses on brain function for theory of mind in typically developing children and its relationship to social cognition and social functioning. Investigating the neural mechanisms underlying social cognitive deficits and social functioning impairment in young adults and children at risk for schizophrenia will contribute to the field’s understanding of the development of this disorder.Psycholog

Attentional control mediates the relationship between social anhedonia and social impairment

Social anhedonia (SA), a trait-like disinterest in social contact and diminished capacity to experience pleasure from social interactions, is consistently associated with social impairments in both healthy and clinical populations. However, the mechanisms underlying the relationship between SA and social impairment are poorly understood. Attentional control, selecting and focusing on relevant information and inhibiting irrelevant, may be one such mechanism. We examined individual differences in SA, attentional control, and social impairment in 108 healthy adults. High SA related to low attentional control and high social impairment. Moreover, attentional control mediated the relationship between SA and social impairment, establishing attentional control as one mechanism underlying aberrations in the fundamental human need for social contact. Although both attentional deficits and social impairment have been separately noted in SA, the relationship between SA, attentional control and social impairment in this non-clinical sample reflects a novel contribution

Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia

Using Fiction to Assess Mental State Understanding: A New Task for Assessing Theory of Mind in Adults

Social functioning depends on the ability to attribute and reason about the mental states of others – an ability known as theory of mind (ToM). Research in this field is limited by the use of tasks in which ceiling effects are ubiquitous, rendering them insensitive to individual differences in ToM ability and instances of subtle ToM impairment. Here, we present data from a new ToM task – the Short Story Task (SST) - intended to improve upon many aspects of existing ToM measures. More specifically, the SST was designed to: (a) assess the full range of individual differences in ToM ability without suffering from ceiling effects; (b) incorporate a range of mental states of differing complexity, including epistemic states, affective states, and intentions to be inferred from a first- and second-order level; (c) use ToM stimuli representative of real-world social interactions; (d) require participants to utilize social context when making mental state inferences; (e) exhibit adequate psychometric properties; and (f) be quick and easy to administer and score. In the task, participants read a short story and were asked questions that assessed explicit mental state reasoning, spontaneous mental state inference, and comprehension of the non-mental aspects of the story. Responses were scored according to a rubric that assigned greater points for accurate mental state attributions that included multiple characters’ mental states. Results demonstrate that the SST is sensitive to variation in ToM ability, can be accurately scored by multiple raters, and exhibits concurrent validity with other social cognitive tasks. The results support the effectiveness of this new measure of ToM in the study of social cognition. The findings are also consistent with studies demonstrating significant relationships among narrative transportation, ToM, and the reading of fiction. Together, the data indicate that reading fiction may be an avenue for improving ToM ability

The neural basis of theory of mind and its relationship to social functioning and social anhedonia in individuals with schizophrenia☆

Theory of mind (ToM), the ability to attribute and reason about the mental states of others, is a strong determinant of social functioning among individuals with schizophrenia. Identifying the neural bases of ToM and their relationship to social functioning may elucidate functionally relevant neurobiological targets for intervention. ToM ability may additionally account for other social phenomena that affect social functioning, such as social anhedonia (SocAnh). Given recent research in schizophrenia demonstrating improved neural functioning in response to increased use of cognitive skills, it is possible that SocAnh, which decreases one's opportunity to engage in ToM, could compromise social functioning through its deleterious effect on ToM-related neural circuitry. Here, twenty individuals with schizophrenia and 18 healthy controls underwent fMRI while performing the False-Belief Task. Aspects of social functioning were assessed using multiple methods including self-report (Interpersonal Reactivity Index, Social Adjustment Scale), clinician-ratings (Global Functioning Social Scale), and performance-based tasks (MSCEIT—Managing Emotions). SocAnh was measured with the Revised Social Anhedonia Scale. Region-of-interest and whole-brain analyses revealed reduced recruitment of medial prefrontal cortex (MPFC) for ToM in individuals with schizophrenia. Across all participants, activity in this region correlated with most social variables. Mediation analysis revealed that neural activity for ToM in MPFC accounted for the relationship between SocAnh and social functioning. These findings demonstrate that reduced recruitment of MPFC for ToM is an important neurobiological determinant of social functioning. Furthermore, SocAhn may affect social functioning through its impact on ToM-related neural circuitry. Together, these findings suggest ToM ability as an important locus for intervention

The Neural Basis of Social Cognition in Typically Developing Children and Its Relationship to Social Functioning

Theory of mind (ToM), the ability to think about the perspectives, beliefs, and feelings of another, develops throughout childhood and adolescence and is an important skill for social interactions. This study examines neural activity in typically developing children during a novel ToM task – the Movie Mentalizing Task– and tests its relations to ToM behavioral performance and social functioning. In this fMRI task, children ages 8–13years (N=25) watched a brief movie clip and were asked to predict a character’s mental state after a social interaction. Engaging in the Movie Mentalizing Task activated the ToM neural network. Moreover, greater neural activity in the ToM network, including the superior temporal gyrus and inferior frontal gyrus, was associated with better behavioral performance on independent ToM tasks and was related to better social functioning, though these results do not survive correction for multiple comparisons. Results offer a new affective theory of mind task for children in the scanner that robustly recruits activity in theory of mind regions

Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals

Social anhedonia (SA) is a debilitating characteristic of schizophrenia, a common feature in individuals at psychosis-risk, and a vulnerability for developing schizophrenia-spectrum disorders. Prior work (Hooker et al., 2014) revealed neural deficits in the ventral lateral prefrontal cortex (VLPFC) when processing positive social cues in a community sample of people with high SA. Lower VLPFC neural activity was related to more severe self-reported schizophrenia-spectrum symptoms as well as the exacerbation of symptoms after social stress. In the current study, psycho-physiological interaction (PPI) analysis was applied to further investigate the neural mechanisms mediated by the VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA exhibited reduced connectivity between the VLPFC and the motor cortex, the inferior parietal and the posterior temporal regions when viewing socially positive (relative to neutral) emotions. Across all participants, VLPFC connectivity correlated with behavioral and self-reported measures of attentional control, emotion management, and reward processing. Our results suggest that impairments to the VLPFC mediated neural circuitry underlie the cognitive and emotional deficits associated with social anhedonia, and may serve as neural targets for prevention and treatment of schizophrenia-spectrum disorders

Altered reward processing following an acute social stressor in adolescents

Altered reward processing is a transdiagnostic factor implicated in a wide range of psychiatric disorders. While prior animal and adult research has shown that stress contributes to reward dysfunction, less is known about how stress impacts reward processing in youth. Towards addressing this gap, the present study probed neural activation associated with reward processing following an acute stressor. Healthy adolescents (n = 40) completed a clinical assessment, and fMRI data were acquired while participants completed a monetary guessing task under a no-stress condition and then under a stress condition. Based on prior literature, analyses focused on a priori defined regions-of-interest, specifically the striatum (win trials) and dorsal anterior cingulate cortex [dACC] and insula (loss trials). Two main findings emerged. First, reward-related neural activation (i.e., striatum) was blunted in the stress relative to the no-stress condition. Second, the stress condition also contributed to blunted neural response following reward in loss-related regions (i.e., dACC, anterior insula); however, there were no changes in loss sensitivity. These results highlight the importance of conceptualizing neural vulnerability within the presence of stress, as this may clarify risk for mental disorders during a critical period of development

In vivo silencing of alpha-synuclein using naked siRNA

<p>Abstract</p> <p>Background</p> <p>Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease <it>post-mortem</it>. Genetic variability in <it>SNCA </it>contributes to risk of idiopathic Parkinson's disease (PD), possibly as a result of overexpression. <it>SNCA </it>downregulation is therefore a valid therapeutic target for PD.</p> <p>Results</p> <p>We have identified human and murine-specific siRNA molecules which reduce <it>SNCA in vitro</it>. As a proof of concept, we demonstrate that direct infusion of chemically modified (naked), murine-specific siRNA into the hippocampus significantly reduces <it>SNCA </it>levels. Reduction of <it>SNCA </it>in the hippocampus and cortex persists for a minimum of 1 week post-infusion with recovery nearing control levels by 3 weeks post-infusion.</p> <p>Conclusion</p> <p>We have developed naked gene-specific siRNAs that silence expression of <it>SNCA in vivo</it>. This approach may prove beneficial toward our understanding of the endogenous functional equilibrium of <it>SNCA</it>, its role in disease, and eventually as a therapeutic strategy for α-synucleinopathies resulting from <it>SNCA </it>overexpression.</p

Ethical decision making: A process influenced by moral intensity

Abstract Understanding the process in which individuals engage in ethical decision making and the factors influencing this process may be important for developing more effective ethics education and leader development programs. This study investigated three components of ethical decision making: moral awareness, moral judgment, and moral intention, and their relationship with five components of moral intensity: Social Consensus, Magnitude of Consequences, Temporal Immediacy, Proximity and Probability of Effect. The results suggest that as individuals face morally charged situations, their awareness of the moral dilemma, judgments about potential consequences, and intention to act are significantly affected by characteristics of the moral situation